Virology The goals of the Virology Program are to continue to identify the mechanisms through which human tumor viruses induce cancer and to use these findings to develop translational studies that target these processes. The major programmatic areas are Immunity, Pathogenesis, Vims:Cell Interactions, and AIDS-associated Cancers: A.) The Immunity group has focused on the development of effective new vaccines for viral infection and cancer, viral vectors for gene delivery, and the identification of the effects of viral infection on innate immunity and inflammation. Alphavimses and corona viruses have powerful effects on innate immunity and their mechanisms to impair this response are under study. Additionally, the effects of EBV and KSHV on interferon regulatory factors and toll-like receptors are under study. B.) The Pathogenesis group analyzes human tumor specimens to identify the viral effects on cell growth and expression and have developed transgenic mice to model the malignancies associated with these viruses. C.) The VimsiCell Interaction's studies have revealed effects of EBV and KSHV on the ubiquitin pathway including the identification of virally encoded deubiquitinases, and have analyzed viral activation of the PI3kinase/Akt/pcatenin and NFKB pathways. D.) The study of AIDS-associated virally induced cancers is expanding and three NCI supplemental grants for the study of AIDS-associated cancers have been recently funded. Experimental translational studies have been initiated to treat AIDS-associated lymphomas and characterize oral HPV infection. Three of the investigators that study human herpesvimses are funded through a Virology Program Project grant with projects that are based on newly developed technologies that are available through the Lineberger Cancer Center shared resources, including the Proteomics Core and Next Generation Sequencing. New members of the Program study viral infections in humanized mouse models, HCV, and human papilloma virus (HPV). The etiologic contributions of the human tumor viruses, EBV, KSH'V, HCV, and HPV will be further analyzed through the study of clinical samples, in vitro transformation systems, and animal models. The future plans for the Program include recruitment of additional investigators in virally-associated cancers and the expansion of specific anti-viral and immuno-therapies for these cancers with specific focus on experimental therapeutics for AIDS malignancies.